Previously Treated CD20+ B-cell Malignancies
Conditions
Brief summary
Ocaratuzumab is a third-generation, fully humanized IgG1 monoclonal antibody (mAb) targeting the CD20 surface marker on normal and malignant B lymphocytes. It has been optimized for an increased binding for CD20 and an enhanced antibody dependent cell medicated cytotoxicity (ADCC) effector function. A previous phase I/II study of intravenously (IV) administered ocaratuzumab in refractory/relapsed follicular lymphoma patients has concluded that ocaratuzumab is safe and well-tolerated at doses up to 375mg/ m2 weekly for four weeks. In this proposed phase I study, ocaratuzumab will be administered subcutaneously to patients with previously treated CD20+ B-cell malignancies. Three dose levels (40 mg weekly x 4 doses, 80 mg weekly x 4 doses, and 80 mg weekly x 8 doses) will be investigated for safety, tolerability, pharmacokinetic, and pharmacodynamic analyses.
Interventions
BIOLOGICALocaratuzumab
Sponsors
Mentrik Biotech, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years; * Histologically confirmed diagnosis of a CD20+ B-cell malignancy; * Received at least one prior treatment regimen;historically documented CD20-positivity is acceptable; * Appropriate for single agent study drug therapy as prescribed by this protocol; * ECOG performance status 0 to 2; * Adequate hematopoietic, renal, and hepatic functions defined as: * Absolute neutrophil count greater than 1000 /mm³ * Platelet count greater than 75,000/mm³ * Hemoglobin greater than 8.5 g/dL * Serum creatinine ≤ 1.5x upper limit of normal * AST, ALT, and total bilirubin ≤ 3x upper limit of normal; * Ability to understand and the willingness to sign a written informed consent document; * Life expectancy of 6 months or greater.
Exclusion criteria
* Anti-CD20 therapy within 4 weeks of enrollment; * Systemic chemotherapy or immunotherapy within 14 days of enrollment; * Chronic systemic steroid therapy defined as prednisone or equivalent 10 mg/day or greater; * Systemic cytotoxic or immunosuppressive therapy to be administered concomitantly while participating on this study; * Active infection, chronic or severe infection requiring ongoing antimicrobial therapy. * Positivity for hepatitis B (defined as HepBs Antigen +), hepatitis C (defined as HepC Antibody +), or HIV; HIV positive patients on antiretroviral therapy will be excluded; * History of allergic reactions attributed to compounds of similar chemical or biologic composition; * Significant cardiac disease (New York Heart Association classes III or IV) or unstable angina despite medication; * Women who are pregnant or breast-feeding; * Women of child bearing potential who are unwilling to use effective contraception for the duration of the study drug administration and 6 months after final dose of drug is administered; * Psychiatric illness/social situations that would limit compliance with study requirements; * Participation in other investigational studies while enrolled on this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters following SC ocaratuzumab administration such as area under the curve, maximum serum drug concentration, and elimination half life | Every office visit throughout the study for up to 12 months |
| Pharmacodynamic profile of B-cell depletion and re-population as measured by CD19+ peripheral blood B lymphocyte count | Baseline, day 1 and 8, 1 mon, 3 mon, 6 mon, and 12 mon post-treatment |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability of SC ocaratuzumab administration as described by the incidence of adverse events such as local injection site reactions or laboratory abnormalities | Every office visit throughout the study for up to 12 months |
| Immunogenicity as measured by the incidence, titre of human anti-human antibody (HAHA) immune response | Baseline, 1 mon, 2 mon, 3 mon, 6 mon, and 12 mon post-treatment |
Countries
United States
Outcome results
None listed